Advances in Biomimetic Nanoparticles for Targeted Cancer Therapy and Diagnosis.

Biomimetic nanoparticles have recently emerged as a novel drug delivery platform to improve drug biocompatibility and specificity at the desired disease site, especially the tumour microenvironment. Conventional nanoparticles often encounter rapid clearance by the immune system and have poor drug-targeting effects. The rapid development of nanotechnology provides an opportunity to integrate different types of biomaterials onto the surface of nanoparticles, which enables them to mimic the natural biological features and functions of the cells. This mimicry strategy favours the escape of biomimetic nanoparticles from clearance by the immune system and reduces potential toxic side effects. Despite the rapid development in this field, not much has progressed to the clinical stage. Thus, there is an urgent need to develop biomimetic-based nanomedicine to produce a highly specific and effective drug delivery system, especially for malignant tumours, which can be used for clinical purposes. Here, the recent developments for various types of biomimetic nanoparticles are discussed, along with their applications for cancer imaging and treatments.

Nanotechnology Approaches in Tackling Cardiovascular Diseases.

Cardiovascular diseases have continued to remain a leading cause of mortality and morbidity worldwide. Poor proliferation capability of adult cardiomyocytes disables the heart from regenerating new myocardium after a myocardial ischaemia event and therefore weakens the heart in the long term, which may result in heart failure and death. Delivery of cardioprotective therapeutics soon after the event can help to protect the heart from further cell death and improve cardiac function, but delivery methods and potential side effects of these therapeutics may be an issue. Advances in nanotechnology, particularly nanoparticles for drug delivery, have enabled researchers to obtain better drug targeting capability, thus increasing the therapeutic outcome. Detailed study of nanoparticles in vivo is useful as it can provide insight for future treatments. Nanogel can help to create a more favourable environment, not only for a sustained delivery of therapeutics, but also for a better navigation of the therapeutics to the targeted sites. Finally, if the damage to the myocardium is too severe for drug treatment, nanopatch can help to improve cardiac function and healing by becoming a platform for pluripotent stem cell-derived cardiomyocytes to grow for the purpose of cell-based regenerative therapy.

PEGylation of Phosphatidylglycerol/Docosahexaenoic Acid Hexosomes with d-α-Tocopheryl Succinate Poly(ethylene glycol)2000 Induces Morphological Transformation into Vesicles with Prolonged Circulation Times.

Considering the broad therapeutic potential of omega-3 polyunsaturated fatty acids such as docosahexaenoic acid (DHA), here we study the effect of PEGylation of DHA-incorporated hexosomes on their physicochemical characteristics and biodistribution following intravenous injection into mice. Hexosomes were formed from phosphatidylglycerol and DHA with a weight ratio of 3:2. PEGylation was achieved through the incorporation of either d-α-tocopheryl succinate poly(ethylene glycol)2000 (TPGS-mPEG2000) or 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy-poly(ethylene glycol)2000 (DSPE-mPEG2000) at a concentration of 1.5 wt %. Nanoparticle tracking analysis, synchrotron small-angle scattering, and cryo-transmission electron microscopy were employed to characterize the nanodispersions. The results show that PEGylated lipids induce a structural transition from an inverse hexagonal (H2) phase inside the nanoparticles (hexosomes) to a lamellar (Lα) phase (vesicles). We also followed the effect of mouse plasma on the nanodispersion size distribution, number, and morphology because changes brought by plasma constituents could regulate the in vivo performance of intravenously injected nanodispersions. For comparative biodistribution studies, fluorescently labeled nanodispersions of equivalent quantum yields were injected intravenously into healthy mice. TPGS-mPEG2000-induced vesicles were most effective in avoiding hepatosplenic clearance at early time points. In an orthotopic xenograft murine model of glioblastoma, TPGS-mPEG2000-induced vesicles also showed improved localization to the brain compared with native hexosomes. We discuss these observations and their implications for the future design of injectable lyotropic nonlamellar liquid crystalline drug delivery nanosystems for therapeutic interventions of brain and liver diseases.

The gut microbiota regulates acute foreign body reaction and tissue repair after biomaterial implantation.

We hypothesized that the host microbiome may influence foreign body responses following biomaterial implantation. To test this, we implanted a variety of clinically relevant biomaterials into germ-free or antibiotic-treated mice. Surprisingly, these mice displayed less fibrous tissue deposition, reduced host cell recruitment to the implant site, and differential expression of angiogenic and inflammatory markers. These observations were reversed upon fecal microbiome reconstitution, confirming a causal role of the host microbiome. In a clinically relevant disease model, microbiome-depleted mice cleared hyaluronic acid and bone marrow mononuclear cells from ischemic hind limb tissues more slowly, resulting in an improved therapeutic response. Findings were confirmed in pigs which showed reduced fibrotic responses to a variety of implanted materials. Lastly, we profiled changes in the host microbiome following material implantation, implicating several key bacteria phyla.

Depletion of gut microbiota improves the therapeutic efficacy of cancer nanomedicine.

Rationale: Gut microbiota plays a crucial role in cancer development and treatment. Studies show that although the gut microbiota is able to promote tumor growth, its presence also improves the efficacy of cancer treatment such as immunotherapy. To date, understanding of the potential impact of the gut microbiota on other treatment modalities such as cancer nanomedicine is still limited. In this study, we aimed to establish the relationship between gut microbiota and cancer nanomedicine, which can potentially open a new path in cancer treatment that combines gut microbiota modulation along with nanotherapeutics. Methods: Mice bearing 4T1 triple-negative breast cancer cells were subjected to gut microbiota modulation by antibiotics (ABX) treatment in the drinking water. Mice given normal water was used for control. The effects of ABX treatment towards gut bacteria was studied by RT-qPCR and 16S next generation sequencing of fecal samples. The mice were then subjected to liposomal doxorubicin (LipoDox) treatment and the amount of nanotherapeutics that accumulated in the tumors was quantified. For therapeutic efficacy, the mice were subjected to ABX treatment and given three injections of LipoDox or saline, while the tumor growth was monitored throughout. Results: Analysis of fecal bacterial content showed that ABX treatment resulted in depletion of gut microbiota. Quantification of LipoDox content revealed significantly increased accumulation in ABX tumor compared to control. Compared to LipoDox treatment alone, we found that combined gut microbiota depletion and LipoDox treatment resulted in augmented long-term anti-tumor efficacy and significantly improved median survival compared to LipoDox only (control vs ABX = 58.5 vs 74 days, p = 0.0002, n = 10 for both groups), with two mice surviving until the end of the experimental end point without experiencing relapse. We also identified the increase in vascular permeability of ABX-treated tumors correlated to for improved therapeutic efficacy and outcome. Conclusion: We showed that gut microbiota depletion led to enhanced tumor vascular permeability, which allowed a larger amount of LipoDox nanoparticles to accumulate in the tumor, leading to better long-term effects. Our results suggest that gut microbiota modulation may be exploited in combination with available nanomedicine-based therapeutics to improve cancer diagnosis, therapeutic efficacy and outcome.

Immune cell shuttle for precise delivery of nanotherapeutics for heart disease and cancer.

The delivery of therapeutics through the circulatory system is one of the least arduous and less invasive interventions; however, this approach is hampered by low vascular density or permeability. In this study, by exploiting the ability of monocytes to actively penetrate into diseased sites, we designed aptamer-based lipid nanovectors that actively bind onto the surface of monocytes and are released upon reaching the diseased sites. Our method was thoroughly assessed through treating two of the top causes of death in the world, cardiac ischemia-reperfusion injury and pancreatic ductal adenocarcinoma with or without liver metastasis, and showed a significant increase in survival and healing with no toxicity to the liver and kidneys in either case, indicating the success and ubiquity of our platform. We believe that this system provides a new therapeutic method, which can potentially be adapted to treat a myriad of diseases that involve monocyte recruitment in their pathophysiology.